Nanowire Field Effect Transistor (FET) sensor technology has demonstrated tremendous potential for point-of-care (POC) applications and has been successfully used for detection of proteins (Cui et al., 2001, Science, 293: 1289-1292), oligonucleotide sequences (Zhang et al., 2008, Nano Lett, 8(4): 1066-1070), cellular function (Stern et al, 2008, Nano Lett, 8(10): 3310-3314), virus detection (Patolsky et al., 2004, Proc Natl Acad Sci, 101(39): 14017-14022) and enzymatic activity (Stern et al., 2010, Small, 6(2): 232-238). Nanowire FET sensors have been used in numerous applications, and have been incorporated into label-free detection systems.
Electronic label-free detection is based on nanosensor surface modification with specific receptors capable of recognizing and binding the desired target molecules. Upon binding, the nanosensor surface potential is changed due to the electric charge present on the bound molecule, which modulates the nanosensor surface potential and thus causes an increase or decrease of carriers and device current (Bergveld, 1981, Sens Actuators, 17-29).
While several qualitative studies have demonstrated the true power of this detection method, the lack of quantitative results diminishes the competitiveness of the BioFET technology with the existing state-of-the-art techniques. A number of previous experiments have been performed on “bottom-up” or chemical vapour deposition (CVD) grown nanowires, but this method suffers from large device-to-device variation in electrical parameters such as threshold voltage, mobility and transconductance (Ishikawa et al., 2009, ACS Nano, 3(12): 3969-3976). Given these fluctuations, individual device calibration is thus required for quantitative analysis, thus eliminating one of the primary advantages of a microfabrication approach, i.e. multiplexing.
Thus, there is a need in the art for biosensors with uniform characteristics and for methods of calibrating the response of biosensors to provide quantitative detection and analysis. The present invention satisfies this unmet need.